Diabetic nephropathy (DN) is a leading cause of morbidity and mortality in diabetic patients representing a huge health and economic burden. Alarming recent data described diabetes as an unprecedented worldwide epidemic, with a prevalence of ∼6.4% of the world population in 2010, while the prevalence of CKD among diabetics was approximately 40%. With a clinical field hungry for novel markers predicting DN, several clinical and laboratory markers were identified lately with the promise of reliable DN prediction. Among those are age, gender, hypertension, smoking, sex hormones and anemia. In addition, eccentric left ventricular geometric patterns, detected by echocardiography, and renal hypertrophy, revealed by ultrasonography, are promising new markers predicting DN development. Serum and urinary markers are still invaluable elements, including serum uric acid, microalbuminuria, macroalbuminuria, urinary liver-type fatty acid-binding protein (u-LFABP), and urinary nephrin. Moreover, studies have illustrated a tight relationship between obstructive sleep apnea and the development of DN. The purpose of this review is to present the latest advances in identifying promising predictors to DN, which will help guide the future research questions in this field. Aiming at limiting this paramount threat, further efforts are necessary to identify and control independent modifiable risk factors, while developing an integrative algorithm for utilization in DN future screening programs.